Adding anthracyclines to taxane-based chemotherapy beneficial in high-risk breast cancer
Key takeaways:
- Patients who received anthracyclines in addition to taxane-based chemotherapy experienced improved survival.
- Patients with a higher recurrence score more likely benefited from anthracyclines.
SAN ANTONIO — The addition of anthracyclines to adjuvant taxane-based chemotherapy improved survival for certain high-risk patients with breast cancer, according to data presented at San Antonio Breast Cancer Symposium.
A higher recurrence score strongly correlated with longer survival after the addition of anthracyclines, with patients who had tumors at least 2 cm in size deriving the greatest benefit.
“A lot of this does correspond to what many practitioners are doing in clinical practice,” Nan Chen, MD, assistant professor of medicine at The University of Chicago, told Healio. “With higher recurrence scores, we’re concerned about greater risk, and we may consider using anthracycline as a way to mitigate some of that risk.
“We also recognize that breast cancer exists on a spectrum and that some of what drives higher scores may be tumor biology that’s more akin to triple-negative disease,” she added. “In triple-negative disease, the benefit of anthracyclines is much more clear than it is in [hormone receptor]-positive [disease], so I don’t necessarily think this was surprising. But I do think this was a good demonstration and hopefully can provide specific guidance to physicians who may be having conversations with their patients in clinic.”
Background and methods
The prior Anthracyclines in Early Breast Cancer trials showed no definitive improvement in invasive DFS for patients with hormone receptor-positive breast cancer who received anthracyclines with a taxane-containing chemotherapy.
Lower-risk patients with hormone receptor-positive/HER2-negative disease typically receive an anthracycline-free regimen, but the potential benefit of anthracyclines for patients with a high recurrence score according to the OncotypeDX genomic test (Exact Sciences) had not been studied.
Chen and colleagues analyzed data from 2,591 patients in the randomized TAILORx study, 437 of whom received taxane and anthracycline/cyclophosphamide (T-AC) or similar regimens, and 2,091 of whom received taxane plus cyclophosphamide chemotherapy (TC).
All patients had been diagnosed with stage I/stage II node-negative, hormone receptor-positive or HER2-negative breast cancer.
Among the T-AC group, 298 (68%) received anthracycline and cyclophosphamide followed by taxane; 59 (14%) received concurrent anthracycline, cyclophosphamide and docetaxel;, and 80 (18%) received other anthracycline plus taxane combinations.
Patients with recurrence scores between 11 and 25 received endocrine therapy or endocrine therapy plus chemotherapy of physicians’ choice. Patients with recurrence scores of 26 or higher received physicians’ choice of chemotherapy.
Patients who received T-AC tended to have a higher recurrence score (mean, 30 vs. 23) and larger tumors (mean, 20 mm vs. 18 mm). They also more often had high-grade tumors (38% vs. 25%).
Researchers compared distant recurrence-free interval (DRFI), recurrence-free interval (RFI), distant RFS (DRFS), RFS and OS, while controlling for variables such as age, recurrence score, grade, tumor size and ER/PR status.
Results
Among patients with recurrence scores over 31, those who received T-AC had improved 5-year outcomes compared with those who received TC. This trend persisted in analyses for DRFI (97.5% vs. 89.4%; adjusted HR = 0.27), DRFS (96.5% vs. 88.3%; adjusted HR = 0.45), RFI (95.7% vs. 87.7%; adjusted HR = 0.31) and RFS (94.6% vs. 86.6%; adjusted HR = 0.45).
Patients who received T-AC also had improved OS at 5-years (97.7% vs. 92.5%; adjusted HR = 0.58).
T-AC did not appear associated with improved DRFI (adjusted HR = 1.12) or DRFS (adjusted HR = 1.09) among patients with recurrence scores lower than 31.
Spline regression estimated benefits of T-AC on DRFI in an increasing fashion as patients’ recurrence score increased, with estimates available for a recurrence score of 20 (adjusted HR = 0.96; 95% CI, 0.53-1.75), 30 (adjusted HR = 0.79; 95% CI, 0.45-1.39), 40 (adjusted HR = 0.6; 95% CI, 0.34-1.05) and 50 (adjusted HR = 0.45; 95% CI, 0.21-0.96).
“We believe that these findings have some implications for clinical care with caution,” Chen said in a press release. “Previous trials have shown the early benefit in recurrence reduction with anthracyclines may be offset by late risk of non-breast cancer deaths such as leukemia, so longer-term follow-up will be needed, and these risks should be discussed with patients before considering anthracycline-based chemotherapy.”
Because the TAILORx study consisted of patients with node-negative disease, Chen said she anticipates next investigating the effect of the addition of anthracyclines to taxane-based chemotherapy in a different patient population.
“One of the first areas we want to look at in the future is how this may fare in a node-positive population, because that would be a higher clinical risk patient population [with] a higher clinical recurrence concern,” Chen told Healio. “Also, we have these novel therapies in the early breast cancer space such as CDK4/6 inhibitors. Those therapies may change the way we think about chemotherapy and anthracyclines for these patients.”
Perspective
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Currently, most people tend to use anthracyclines in this patient population anyway. What this study provides is a comparison that adds to that body of knowledge that those patients may need. We’re doing this for the most part, but this is a vigorous demonstration that there is a benefit for the addition of anthracyclines for patients with a high recurrence score.
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Chen N, et al. Abstract GS3-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-13, 2024; San Antonio.